CPE; has been used for suicide gene therapy for selective treatment of claudin-3-and-4-overexpressing tumors (Walther et al., 2011). It can be used as an oncoleaking/tumor eradication agent as this pore-forming protein exerts specific and rapid toxicity towards claudin-3- and -4-overexpressing cancers (Pahle et al. 2015). The crystal structure of Clostridium perfringens enterotoxin displays features of beta-pore-forming toxins (Kitadokoro et al., 2011). The N-terminal region (nCPE) mediates the cytotoxic effect through pore formation in the plasma membrane of the mammalian host cell. The C-terminal region (cCPE) binds to the second extracellular loop of a subset of claudins, Claudin-3 and claudin-4, with high affinity (Veshnyakova et al., 2010). cCPE is not cytotoxic but is a potent modulator of tight junctions.

The β-barrel pore-forming toxin (PFP), Monalysin. The soluble monomer is cleaved to yield oligomeric pores. The structure of a cleaved form lacking the transmembrane domain has been solved by x-ray crystalography and cryo-EM (PDB#4MJT; Leone et al. 2015). The structure displays an elongated shape, resembling those of beta-pore-forming toxins such as
aerolysin, but it lacks the receptor binding domain. Pro-monalysin forms a stable doughnut-like 18-mer complex
composed of two disk-shaped nonamers held together by N-terminal swapping of the pro-peptides. This is in contrast with the monomeric pro-form of the other beta-PFTs that are receptor-dependent for membrane interaction. The membrane-spanning region of pro-monalysin is fully buried in
the center of the doughnut, suggesting that upon pro-peptide cleavage, the two disk-shaped nonamers
can - and have to - dissociate to leave the transmembrane segments free to deploy and lead to pore
formation. In contrast with other toxins, the delivery of 18 subunits at once, nearby the cell
surface, may be used to by-pass the requirement for a receptor-dependent concentration to reach the
threshold for oligomerization into the pore-forming complex (Leone et al. 2015).

Putative toxin, SmlA of 283 aas. Deleting the encoding gene gives rise to slime molds that can only form small aggregates. May regulate the secretion or processing of a secreted factor that regulates aggregate size.